A variety of projects are underway to improve the safety and efficacy of therapy with cancer chemotherapeutic agents, including antifolates, nitrosoureas, adriamycin, and 5-fluorouracil. Pharmacokinetic studies have allowed the use of high dose methotrexate with little toxicity, with the help of monitoring of plasma levels and adjustment of leucovorin dosage. In vitro studies are being conducted to elucidate the possible role of drugs which expedite methotrexate transport. The biological properties of nitrosourea derivatives are under study and a new non-myelosuppressive analog, chlorozotocin, will enter trials in the coming year. Methods are being developed to assay a variety of drugs by competitive binding techniques, and these methods are being used to examine the physico-chemical features of binding of substrate and inhibitor in detail.